Two (2) of the leading issues facing healthcare providers and policymakers in the sub-Saharan Africa are the prevention and treatment of opportunistic infections, and the implementation of anti-retroviral therapy strategies that maximize limited resources and meet local needs. In this revised proposal, the candidate will apply epidemiologic and mathematical modeling tools to better understand the profile of Ols in South Africa, and to model outcomes and cost-effectiveness of 2 interventions that should have important implications for the optimization of Ol prophylaxis and antiretroviral therapy. 3 Specific Aims are proposed: 1) To use mixed effects modeling to estimate the incidence rates of specified opportunistic infections within clinically important CD4 cell count strata in an HIV-infected cohort in Cape Town, South Africa. 2) To develop a decision-analytic model to project clinical outcomes, costs, and cost-effectiveness of primary antifungal prophylaxis in South Africa, using the natural history data derived in Aim 1. 3) To develop a decision-analytic model to project the clinical, virologic and cost-effectiveness outcomes of NNRTI versus Pi-based ART regimens in South African women with a history of peri-partum nevirapine exposure. The candidate is a 3rd year infectious disease fellow at Massachusetts General Hospital working toward a goal of a becoming an independently funded physician investigator in Infectious Disease research. He has a background in epidemiology and through experiences at WHO and in Africa has a clear idea of important clinical and policy questions in the region. This proposal outlines a research plan to address these questions using new skills he will acquire in longitudinal data analysis and decision sciences. The applicant will benefit from working within the interdisciplinary Cost-Effectiveness of Preventing AIDS Complications group, and from regular input from his Research Advisory Committee. He is mentored by two senior investigators with an extremely strong record of mentoring junior investigators and guiding them to become successful physician scientists.